Effect Of Atmospheric Fine Particulate Matter(PM_2.5) On The Prognosis Of COPD Patients And The Regulation Of Inflammasomes

Part I ObjectiveWe performed the study to explore the correlation between short-term PM_2.5 exposure and COPD hospitalizations and mortality.MethodsComprehensive and systematic searches were performed in the electronic reference databases（PubMed, EMBASE, Google Scholar, Ovid, and Web of Science） with specific search terms and selection criteria for relevant studies. Summary odds ratios（ORs） and 95% confidence intervals（CIs） were performed to evaluate the relationship between short-term PM_2.5 exposure and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using random-effect model and fixed effect model in COPD hospitalizations and mortality, respectively.ResultsThe search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies for the mortality meta-analysis during the period. A 10 ug/m3 increase in daily PM_2.5（lag days 0-7） was associated with a 3.1%（95% CI: 1.6%-4.6%） increase in COPD hospitalizations, and a 2.5%（95% CI: 1.5%-3.5%） increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM_2.5 exposure and COPD hospitalizations and mortality.ConclusionsOur combined analysis indicated that short-term exposure to 10 μg/m3 increment of ambient PM_2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate the mechanism by which PM_2.5 induces activation of cellular processes promoting COPD exacerbations.Part IIObjectiveTo investigate the effect of PM_2.5 on the NLRP3 inflammasomes via mice model exposed PM_2.5.MethodsIn this study, C57 BL / 6 mice（wild type, WT） and NLRP3 knockout mice（NLRP3-/-） were divided into control group, experimental group for instillation of 200 mg PM_2.5 dissolved in 50 ml sterile saline or saline alone. After the instillation, the mice were sacrificed 4, 24 and 72 hours. Blood or bronchoalveolar lavage fluid（BALF） samples were collected for the analysis of the level of interleukin-1β（IL-1β）, IL-18,IL-6, Tumor Necrosis Factor-α（TNF-α）, IL-17 and total protein. At the same time, the pulmonary pathology was also analyzed. Graph-Pad prism 5.0 was used for statistical analysis.Results1. Histopathological estimate of lung sections: lung tissues structure in control group showed normal findings.The pulmonary pathological slide of wild-type mice exposed to PM_2.5 showed alveolar wall congestion, interstitial thickening and inflammatory cell infiltration, and these manifestations were most evident at 24 hours. However, mild inflammatory reaction and tissue damage were found in the lung tissue of NLRP3-/- mice which were exposed to PM_2.5.2. Compared with the control group, the level of total cell counts, neutrophil and macrophage numbers significantly increased in PM_2.5 exposure groups.3. Changes of the level of IL-1β and IL-18 in BALF and serum: compared to the other three groups mice at the same time point, the level of IL-1β and IL-18 in BALF and serum significantly increased the wild-type mice exposed to PM_2.5, and these manifestations are most evident at 24 hours（P<0.05）.4. Changes of the level of TNF-α, IL- 6 and IL-17 in BALF: Compared with the control group, the level of TNF-α, IL- 6 and IL-17 in BALF were significantly increased in PM_2.5 exposure groups. However, compared with PM_2.5 exposure group at each time point, the difference was not statistically significant.Conclusions1. Atmospheric fine particulate matter may induce inflammatory injury of respiratory system in mice by activating NLRP3, and the degree of damage was most obvious at 24 hours.2. PM_2.5 caused respiratory damage, which can lead to the destruction of the structure of normal lung tissue in mice.